Human disease conditions are often very complex due to disturbed interdependencies inside the human body rather than to the impairment of a single cell function. Cell culture models are therefore not sufficient as a model system: full information about human disease conditions can only be obtained from the analysis of a whole animal organism. This is particulariy important in complex systems where cultured cells are not able to model physiological processes. The laboratory mouse is the closest organism to humans that can be easily studied by genetic manipulation. The ultimate goal of many IDDRC projects is to understand the genetic basis of abnormal brain development and/or mental retardation/development disabilities in humans. To achieve this goal many IDDRC investigators, require the generation of genetically modified mice with specific mutations in the germ line and somatic tissues to study the roles of genes In vivo. The core will allow investigators to generate special alleles permitting conditional deletions and conditional rescues studies. Such conditional alleles are not currently available through any other resource. Given that several IDD have already exhibited the potential of reversibility with re-establishment of gene expression, the ability to create mouse models that permit testing for recovery is critical as groups pursue pathogenesis and interventional studies. In addition to conditional studies, targeting of non-coding miRNAs is in demand to gain insight into post transcriptional regulation of various IDD genes. Thus this core augments the large scale efforts to provide knockout alleles for every mouse gene. The procedures necessary for the manipulation of ES cells and the creation of GEM are capital intensive and technically challenging. Dedicated and experienced staff and costly equipment are required to produce mutants in timely cost-effective manner. The ES Core makes it possible for IDDRC investigators to quickly and efficiently obtain mouse models for research relating to developmental disabilities. The Core also provides an invaluable service to many non-IDDRC investigators throughout Baylor and throughout the United States.